CD40在瘤微环境中经历部分内皮细胞-介质细胞过渡的内皮细胞子集中得到表达
Kazuki Takahashi1,2, Miho Kobayashi1, Hisae Katsumata1
1Department of Biochemistry, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
Cancer science
|December 19, 2023
概括
转化生长因子-β (TGF-β) 通过内皮-介质细胞过渡 (EndoMT) 驱动瘤的进展. 研究人员将CD40确定为部分EndoMT的标记物,揭示了其在抑制完全过渡中的作用,并提供了新的治疗点.
科学领域:
- 细胞生物学 细胞生物学
- 癌症研究 癌症研究
- 分子生物学分子生物学
背景情况:
- 瘤的进展和转移涉及内皮-介质细胞过渡 (EndoMT).
- 部分EndoMT状态,混合内皮/介质细胞表型,由于缺乏特定标志物,人们对其了解甚微.
- 转化生长因子-β (TGF-β) 是EndoMT的一个关键诱导因子.
研究的目的:
- 调查TGF-β信号在EndoMT中的作用.
- 开发一个可视化和分析EndoMT阶段的系统.
- 确定部分EndoMT的新型标记物并阐明它们的功能.
主要方法:
- 利用人类口腔癌细胞异种移植小鼠模型研究TGF-β抑制EndoMT.
- 建立了一个新的EndoMT报告器内皮细胞 (EMREC) 系统来可视化EndoMT进展.
- 在人类瘤中进行了多个EndoMT阶段的基因分析和单细胞RNA测序.
主要成果:
- 在小鼠模型中,抑制TGF-β信号的抑制抑制了EndoMT.
- CD40被确定为部分EndoMT的特定标志物,在中间阶段上调,但在全部EndoMT下降.
- 在人类瘤中,CD40表达在具有内皮细胞和中皮细胞标记物的细胞中得到了丰富.
- 减少CD40表达增强了TGF-β诱导的EndoMT,表明部分抑制作用.
结论:
- CD40是部分EndoMT的新型标记物,在调节过渡到完全EndoMT的过程中发挥作用.
- 了解CD40的功能,可以了解EndoMT的机制.
- 这些发现支持开发针对癌症进展和转移的EndoMT向治疗方法.
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